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First-line immuno-chemotherapy is standard for advanced biliary tract cancer (BTC), but outcomes vary substantially, necessitating longitudinal monitoring and treatment adaptation. We aimed to develop models that dynamically update survival predictions using evolving clinical data to support real-time prognostic stratification. We analysed patients with advanced BTC receiving first-line immuno-chemotherapy across eight centres. Cohorts comprised development, internal validation, two retrospective external validation, and one prospective external validation sets. The Bayesian joint model iDREM-BTC integrated baseline clinical and imaging variables with serial C-reactive protein, carbohydrate antigen 19-9, and total bilirubin measurements. iDREM(Pro)-BTC additionally incorporated baseline immunohistochemical and genomic data. Performance was assessed using dynamic area under the curve (AUC), calibration, and comparisons with baseline Cox models; interpretability was examined by ablation analysis (ClinicalTrials.gov: NCT06849193). Among 2314 patients (n=841, 360, 327, 284, and 502, respectively), machine learning identified age, ECOG performance status, tumour burden, tumour stage, and the three longitudinal biomarkers as mortality predictors. iDREM-BTC achieved overall dynamic AUCs of 0·730 (95% CI 0·689-0·794), 0·718 (0·670-0·778), 0·755 (0·707-0·808), 0·705 (0·639-0·773), and 0·745 (0·691-0·802), respectively. Discrimination improved over follow-up in all cohorts, with AUCs increasing from 0·633-0·705 at baseline to 0·778-0·810 at 6 months. iDREM(Pro)-BTC showed higher discrimination in development (n=628; AUC 0·807 [0·781-0·839]) and retained performance in external validation (n=281; 0·718 [0·669-0·787]). Exploratory matched analyses showed overall-survival separation among iDREM-BTC-defined high-risk patients; findings for iDREM(Pro)-BTC were directionally similar but not statistically significant. iDREM-BTC and iDREM(Pro)-BTC provide dynamically updated survival estimates during first-line immuno-chemotherapy and support individualized prognostic stratification, potentially informing treatment adjustment across diverse patient populations and immuno-chemotherapy regimens in clinical practice. We developed the Individualized Dynamic Risk Estimation Model for biliary tract cancer (iDREM-BTC), a novel prognostic prediction and treatment recommendation system trained on data from 841 patients. The model demonstrated robust performance across multiple validation cohorts including 1473 patients. By integrating baseline Cox models with three mixed models incorporating longitudinal biomarkers (C-reactive protein level, carbohydrate antigen 19-9 level, and total bilirubin grade), iDREM-BTC enables real-time, accurate prognostic predictions, risk stratification, and treatment adjustments. The enhanced version, iDREM(Pro)-BTC, further incorporates immunohistochemistry and genomic markers, improving predictive latency while maintaining dynamic modelling advantages. iDREM-BTC and iDREM(Pro)-BTC can serve as valuable bedside resources for clinicians in the routine monitoring and treatment of patients with BTC. These models have also been integrated into an online platform as a research deployment. NCT06849193.

We previously demonstrated that reducing the caloric load of a model drink from 30 g (10 %) sucrose to 21 g (7 %), while maintaining sweetness level with the taste modifier hesperetin, lowered postprandial glucose fluctuations and energy intake at an ad libitum breakfast. However, the contribution of the reduction of the caloric load compared to the addition of hesperetin remained unclear. We hypothesized that independent of participants' sex, the reduction of carbohydrate content is decisive for the glycemic and appetite and sweet craving responses. In a single-blinded, randomized crossover study with 39 healthy adults (21 female), we compared a 10 % sucrose solution, an equi-sweet 7 % sucrose solution containing hesperetin, and a less sweet 7 % sucrose solution with respect to postprandial glucose and incretin responses, as well as energy intake, taking sex-specific differences into account. Females showed lower glucose peaks after both sucrose-reduced drinks (without hesperetin: &#x394; 59 &#xb1; 17 %, p < 0.01; with hesperetin: &#x394; 50 &#xb1; 17 %, p < 0.05), whereas male responses were similar independent of the carbohydrate content. The equi-sweet treatments similarly increased GLP-1 in females (&#x394; 100 &#xb1; 36 %, p < 0.05), but not in males. In contrast, GIP levels rose in men only (&#x394; 177 &#xb1; 65 %, p < 0.05) following the equi-sweet treatments. Despite lower appetite and sweet craving ratings after the sugar-reduced treatments across sexes, subsequent energy intake at an ad libitum breakfast was not significantly different between treatments. These results indicate sex-specific metabolic responses and suggest that lowering sucrose content while maintaining sweetness preserves satiety signaling, without affecting subsequent energy intake at an ad libitum breakfast in both male and female individuals.

Buprenorphine is widely prescribed for opioid use disorder (OUD). In 2022, the U.S. FDA issued a safety warning on dental diseases associated with buprenorphine. While reports implicate increased caries risk, the microbial mechanisms remain unclear. To evaluate whether buprenorphine directly modulates Streptococcus mutans (S. mutans) virulence traits relevant to cariogenesis. S. mutans UA159 were exposed to buprenorphine. Planktonic growth, acidogenicity, acid tolerance, aggregation, and carbohydrate utilization were assessed. Biofilm biomass and extracellular polymeric substance (EPS) production were quantified in hydroxyapatite disc-based monospecies and saliva-derived microcosm models. Biofilm architecture was evaluated using fluorescence in situ hybridization (FISH). The expression of competence- and biofilm-associated genes (comC, comX, gcrR, gtfB, and gtfC) was measured by RT-qPCR. Buprenorphine did not affect planktonic growth, acid production, or carbohydrate metabolism. However, it increased biofilm biomass and EPS production. FISH imaging revealed denser matrix-rich biofilms with closer spatial integration of S. mutans. Gene expression showed upregulation of comC, comX, gcrR, gtfB, and gtfC, indicating enhanced quorum sensing, stress adaptation, and matrix synthesis. Buprenorphine promoted a biofilm-specific virulence program in S. mutans, fostering thicker, EPS-rich biofilms without altering planktonic physiology. These findings provide a mechanistic rationale for buprenorphine's association with caries risk. Buprenorphine triggered biofilm-specific virulence responses in Streptococcus mutans, increasing biofilm mass and extracellular matrix production without affecting growth or metabolism in planktonic culture. These mechanistic findings support clinical observations of severe caries in patients receiving buprenorphine therapy and underscore the need for proactive oral-health prevention in this population, as highlighted by the 2022&#x2009;U.S. Food and Drug Administration safety warning.

Some studies have explored associations between physical activity (PA) and hypoglycaemia in real-life in type 1 diabetes (T1D) but without fully accounting for two major confounders, diet and insulin. We aimed to identify thresholds of PA characteristics, insulin, and carbohydrates associated with dysglycaemia across the exercise-recovery cycle in children with T1D. Continuous glucose monitoring and accelerometry data, self-reported PA sessions (timing, duration and perceived intensity), diet (timing, type and quantity; optional photographs) and insulin data (doses and timing; corrective/meal boluses and basal insulin) were collected in 36 children with T1D (11.9&#x2009;&#xb1;&#x2009;3.3&#x2009;years, injections or open-loop pumps) over seven free-living days. Accelerometer data were analysed for periods corresponding to self-reported PA sessions. Ensemble machine-learning models classified hypoglycaemia (<&#x2009;70&#x2009;mg/dL) and hyperglycaemia (>&#x2009;180&#x2009;mg/dL) during three phases: PA, 2-h post-exercise (early recovery), overnight. Shapley analysis identified risk and protection thresholds of features with high importance. Models achieved moderate to strong performance (AUC: 0.65-0.99; F1-score: 0.62-0.95) across outcomes and phases. Insulin boluses >&#x2009;11% of total daily dose within 4-h pre-exercise and >&#x2009;17% during early recovery were associated with hypoglycaemia risk during PA and early recovery respectively. Carbohydrate intake showed collinearity with insulin, resulting in complex associations with glycaemia. Self-reported PA >&#x2009;80&#x2009;min was associated with hypoglycaemia risk during PA, while accumulating >&#x2009;15&#x2009;min of accelerometer-derived vigorous PA was actually protective against early recovery hypoglycaemia. Multiple daily sessions were associated with nocturnal hyperglycaemia protection. Phase-specific thresholds across exercise and insulin domains associated with exercise-related dysglycaemia were identified.

Lipids in food waste (FW) are promising biofuel precursors, but their recovery from slurry-type FW is limited by entrapment within carbohydrate-protein-solid matrices and emulsion-like structures. This study developed a short-term pre-fermentation pretreatment strengthened by a mixed acidifying inoculum to improve intrinsic lipid recovery before thermal centrifugation. In laboratory tests, inoculated pre-fermentation increased lipid yield by 36.3% relative to the initial slurry and recovered 97.8% of the Soxhlet-determined total solvent-extractable lipid content after 24&#x202f;&#x202f;h. Particle refinement, viscosity reduction, total organic carbon release, lactate accumulation, pH decline, and Lactobacillus dominance indicated that hydrolysis-assisted acidification disintegrated the slurry matrix and improved lipid accessibility. Recovered lipids also showed moderate compositional shifts, including increased saturation, slight C8-C16 enrichment, and minor branched-chain fatty acids, suggesting limited microbial effects on the recovered lipid profile. Full-scale validation at a 600 tonnes/day FW treatment facility achieved a 13.9% lipid-yield increase under an 8&#x202f;&#x202f;h retention time and lower inoculum dosage, demonstrating practical applicability in an operating wet-thermal recovery line. An incremental cost-benefit estimate indicated a positive annual net benefit under conservative assumptions. Overall, inoculation-strengthened pre-fermentation provides a low-retrofit and process-compatible strategy for enhancing FW lipid recovery within existing treatment chains.

Carbohydrates are crucial for plant growth and serve as fundamental energy sources, regulated by multiple factors. In tomato, development is closely linked to hormone-mediated sugar metabolism. Although jasmonic acid (JA) is known to function in signaling and growth regulation, its specific role in sugar metabolism remains unclear. This study demonstrated that JA signaling negatively regulates tomato seedling growth. Exogenous application of the JA activator MeJA suppressed growth, whereas the JA inhibitor DIECA and the JA synthesis mutant spr2 promoted it. Further analysis revealed that JA impaired growth by inhibiting photosynthesis-reducing photosynthetic pigment content and efficiency. MeJA treatment increased fructose and glucose levels but decreased sucrose and starch. These changes resulted from downregulated sucrose synthase (SlSS, SlSPS) activity and expression, alongside upregulated acid invertase (SlAI, SlNI) activity and SlTIV1 expression. Thus, JA restricted tomato seedling growth by suppressing photosynthesis and promoting soluble sugar accumulation. Transcriptome analysis identified SlEXPA8, a JA-responsive expansin gene. JA signaling downregulated SlEXPA8 expression; silencing SlEXPA8 impaired photosynthesis, reduced activities of sucrose-metabolizing enzymes, and lowered sucrose and starch levels, inhibiting seedling growth. Overexpression of SlEXPA8, however, enhanced growth. EMSA, ChIP, GUS, and LUC assays confirmed that SlMYC2 directly bound the SlEXPA8 promoter and regulated its transcription. These findings uncovered a mechanism by which JA signaling modulated sugar metabolism via expansin proteins, offering insights for targeted genetic improvement of tomato seedling vigor.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia and associated carbohydrate, protein, and lipid metabolism disturbances. Poor glycemic control exacerbates the risk of numerous complications, including cardiovascular diseases. Although the oral cavity is among the systems affected by diabetic pathology, its potential to reflect systemic lipid metabolism and cardiovascular risk remains unclear. This study investigated correlations between biochemical lipid markers and thermal parameters obtained from infrared imaging of the tongue to evaluate cardiovascular risk in T2DM patients. The study cohort comprised 29 individuals with T2DM and 12 healthy controls, following application of inclusion and exclusion criteria. Lipid profile parameters and related ratios were analyzed alongside thermal measurements recorded 2 and 10 min after oral cavity cooling. Statistically significant positive correlations were identified between tongue surface temperature and lipid-related ratios at 2 min: triglycerides (TG) (r = 0.47, p = 0.002), total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio (r = 0.55, p < 0.001), and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio (r = 0.54, p < 0.001). No significant correlations were observed between glycated hemoglobin (HbA1c), TC, or LDL-C and temperature parameters (p > 0.05). These findings suggest that thermographic assessment of tongue surface temperature may provide a non-invasive biomarker reflecting lipid metabolism alterations and cardiovascular risk in T2DM patients, supporting its potential utility in early disease diagnosis.

The humid climate and frequent rainfall during the harvest season substantially hinder the utilization of triticale as feed. Although ensiling technology can effectively preserve nutrients, its fermentation quality depends on complex microbial interactions, the core mechanisms of which remain unclear. This study proposes and validates the hypothesis that "bacterial-fungal synergy" can enhance silage fermentation. By inoculating triticale silage with Aspergillus niger (AN), Lactiplantibacillus plantarum (LP) or their combination (ANLP) and performing multi-omics analyses, the mechanism underlying this synergistic effect was systematically elucidated in this study. Compared with the control treatment, triticale silage inoculated with ANLP presented significant decreases in the neutral detergent fiber (NDF), acid detergent fiber (ADF), and ammonia nitrogen (NH3-N) contents and significant increases in the water-soluble carbohydrate (WSC), crude protein (CP), and lactic acid (LA) contents (P&#x2009;<&#x2009;0.05). More crucially, ANLP treatment specifically enriched Delftia, indicating a special functional role for this bacterium in triticale silage. Further metabolomic and correlation analyses revealed that the synergy between A. niger and L. plantarum not only promoted the proliferation of Delftia but also activated the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. This activation drove the synthesis of phenolic acid compounds with antimicrobial and antioxidant activities, such as coumaric acid and indole derivatives. These bioactive metabolites effectively inhibited the growth of harmful microorganisms. In vitro digestibility trials confirmed that the ANLP-treated group achieved the highest dry matter and protein degradation rates, thereby validating the pathway from the microbial mechanism to end-use feed value. Overall, the synergistic effects of bacteria (L. plantarum) and fungi (A. niger) can improve the fermentation quality and nutritional content of triticale by promoting amino acid metabolism and increasing the production of bioactive substances, providing a new strategy for increasing its utilization as a feed resource for ruminants.

Spirulina's valuable properties are often overshadowed by its off-flavour. This study demonstrates that microencapsulation using maltodextrin as wall material effectively addresses these challenges. The encapsulated spirulina (ES1) exhibited good encapsulation efficiency (49.70%) and yield (40.55%), with low wettability (0.08&#x2009;&#xb1;&#x2009;0.03gmin-1) and hygroscopicity (6.16&#x2009;&#xb1;&#x2009;0.18%). Significant composition changes were observed in ES1, including total lipids (6.22&#x2009;&#xb1;&#x2009;0.50g 100&#x2009;g-1), carbohydrates (51.97&#x2009;&#xb1;&#x2009;0.75g 100&#x2009;g-1), moisture (6.42&#x2009;&#xb1;&#x2009;0.24g 100&#x2009;g-1), protein (31.59&#x2009;&#xb1;&#x2009;0.11g 100&#x2009;g-1), ash (3.78&#x2009;&#xb1;&#x2009;0.85g 100&#x2009;g-1) and water activity (0.23&#x2009;&#xb1;&#x2009;0.01Aw). Phytopigments, such as chlorophyll a (32.02&#x2009;&#xb1;&#x2009;0.15&#x2009;mg/g), chlorophyll b (23.12&#x2009;&#xb1;&#x2009;0.30&#x2009;mg/g), total carotenoids (3.13&#x2009;&#xb1;&#x2009;0.00&#x2009;mg/g), c-phycocyanin (17.78&#x2009;&#xb1;&#x2009;0.26&#x2009;mg/g), as well as vitamin B9 (0.5937&#x2009;&#xb1;&#x2009;0.52&#x2009;&#xb5;g/g) and antioxidant activity (25.21&#x2009;&#xb1;&#x2009;3.29%), were well retained. The microcapsules displayed a mean particle size of 2.18&#x2009;&#xb1;&#x2009;2.91&#x2009;&#xb5;m with a PDI of 0.795&#x2009;&#xb1;&#x2009;0.03. Morphological and structural analyses (SEM-EDS, FTIR, XRD, UV-Vis) confirmed electrostatic interactions within the wall matrix, promoting amorphization and stability. Overall, spray-drying microencapsulation of spirulina with maltodextrin effectively improved storage stability by lowering water activity.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease shaped by genetic susceptibility and environmental triggers, particularly the microbiota. Numerous studies have documented substantial structural differences in the oral-gut microbiota between patients with RA and healthy individuals. Emerging evidence suggests that upregulation of specific pathobionts-including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella copri-coupled with autoantigen mimicry and inflammatory cascades, may contribute to RA initiation at extra-articular sites. Conversely, several immunoregulatory bacterial species, such as Bacteroides fragilis, Prevotella histicola, and Clostridium spp., are depleted in patients with RA. Importantly, nutritional factors (including, minerals, vitamins, fiber, flavonoids and polyphenols) and dietary patterns (e.g., Western diet, high-fat diet, Mediterranean diet, fasting, protein- or carbohydrate-rich diets) profoundly shape oral-gut microbial composition, and dietary interventions can either potentiate or suppress these microbial populations. Accordingly, recent management strategies have focused on manipulating dysbiosis through probiotic supplementation (e.g., immunomodulatory Lactobacillus strains), fecal microbiota transplantation (FMT), antibiotic administration, and targeted nutritional interventions that support probiotic efficacy and restore eubiosis. This review discusses the characteristic microbiota structure in patients with RA and evaluates emerging therapeutic strategies-FMT, antibiotics, probiotics, and nutrition-as integrated approaches for RA management.

Diabetes is a chronic metabolic disease characterised by high glucose levels and altered carbohydrate and lipid metabolism, affecting an increasing number of people worldwide. Spain ranks fifth among European countries with the highest incidence of diabetes. Hyperglycaemia causes damage to numerous cell types, including keratinocytes and fibroblasts in the skin. Dermatological manifestations appear in more than 30% of cases of diabetes at the onset of the disease and in up to 100% during the course of the disease. This makes skin examination of patients particularly important, as early treatment of diabetes can slow the progression of the disease and improve its prognosis. In addition, some dermatological changes may alert us to suboptimal metabolic control of previously known diabetes. Some lesions are associated with insulin resistance, others are due to fungal or bacterial infections, there are also alterations due to diabetes itself or to chronic complications of diabetes; finally, there are lesions due to pharmacological treatment of the disease and to devices such as insulin infusion pumps and sensors for interstitial glucose measurement. Knowing and recognising dermatological changes is therefore essential in our daily work, because they guide us towards a better management of the disease and its causes. La diabetes es una enfermedad metab&#xf3;lica cr&#xf3;nica caracterizada por niveles altos de glucosa y un metabolismo alterado de los carbohidratos y de los l&#xed;pidos, que afecta a un n&#xfa;mero creciente de personas en todo el mundo. Espa&#xf1;a ocupa el quinto lugar entre los pa&#xed;ses europeos con mayor incidencia de diabetes. La hiperglucemia provoca da&#xf1;os a numerosos tipos celulares, entre los que se encuentran los queratinocitos y los fibroblastos presentes en la piel. Las manifestaciones dermatol&#xf3;gicas aparecen en m&#xe1;s del 30% de los casos de diabetes al inicio de la enfermedad y hasta en el 100% durante el transcurso de la misma. Ello hace especialmente importante la exploraci&#xf3;n de la piel de los pacientes, ya que el tratamiento precoz de la diabetes puede enlentecer la progresi&#xf3;n de esta y mejorar su pron&#xf3;stico. Adem&#xe1;s, algunas alteraciones dermatol&#xf3;gicas nos pueden alertar de un sub&#xf3;ptimo control metab&#xf3;lico de una diabetes previamente conocida.Hay lesiones que est&#xe1;n asociadas a la insulinorresistencia, otras son debidas a infecciones f&#xfa;ngicas o bacterianas; tambi&#xe9;n existen alteraciones debidas a la diabetes en s&#xed; misma o a complicaciones cr&#xf3;nicas de esta; finalmente hay lesiones debidas al tratamiento farmacol&#xf3;gico de la enfermedad y a dispositivos como las bombas de infusi&#xf3;n de insulina y los sensores para la medici&#xf3;n de la glucosa intersticial. Conocer y reconocer las alteraciones dermatol&#xf3;gicas es, por tanto, esencial en nuestro trabajo diario, porque nos orientan hacia un mejor manejo de la enfermedad y de las causas que la producen.

Early-life sex identification technologies are making sex-specific management increasingly feasible in broiler production, yet limited information exists on how males and females differ in the development of their gut ecosystem. While sex-related variation in growth rate and endocrine physiology is well established, much less is known about potential differences in gut morphology, barrier function, microbiota assembly, and intestinal gene expression during the starter period, where early performance divergence between males and females begins to emerge. A clearer understanding of these early-life processes is essential to refine sex-specific nutrition and management strategies. Therefore, this study investigated sex-related differences in gut morphology, intestinal permeability, microbiota composition and predicted functionality, as well as ileal gene expression related to nutrient transport, barrier function, immune response, and metabolic signaling in broilers at 7, 14, and 21&#xa0;days of age. Body weight followed a typical early-life pattern and differed between sexes only at d 21, when males were heavier. Gut morphology matured similarly in both sexes, whereas gut permeability declined with age and was lower in males at d 20, suggesting a slightly tighter intestinal barrier. Microbiota structure was predominantly shaped by age, but sex-related divergence emerged with maturation from d 14 onward, especially in the cecum: males were enriched in strict anaerobic fermenters and carbohydrate-degradation/short-chain fatty acid (SCFA)-related pathways, while females showed higher abundance of Romboutsia, Flavonifractor, and other taxa linked to proteolytic metabolism and the degradation of aromatic amino acid-derived compounds. Gene expression was mainly driven by age, yet consistent sex-specific transcriptional signatures were revealed. Males were more associated with nutrient transport (e.g.,&#xa0;SLC15A1, SLC30A1, SLC5A1) and epithelial functional maturation profiles (e.g., CDX) over time, whereas females were more associated with tight-junction integrity (e.g., OCLN) and amino-acid sensing/transport markers (e.g., T1R1, SLC3A1). Cecal SCFA concentrations were measured at d 21, yet no differences were found. Overall, gut development was largely age-driven, but sex-specific differences in barrier function, microbiota composition and function, and epithelial gene expression emerged with maturation, without differences in gut morphology or luminal SCFA concentrations.

Although a substantial body of evidence indicates that food insecurity is positively associated with obesity, the underlying mechanisms of this relationship remain unclear. This cross-sectional study, conducted on 859 individuals, aimed to examine the association between food insecurity and obesity. Food insecurity was assessed using the Household Food Insecurity Access Scale (HFIAS), which was developed by the Food and Nutrition Technical Assistance (FANTA) project under the United States Agency for International Development (USAID). Factors influencing food insecurity and the role of food insecurity in obesity were evaluated. The mean age of the participants was 34.70&#x2009;&#xb1;&#x2009;13.84&#x2009;years (range: 18-85). The prevalence of obesity was 4.5% in the mildly food-insecure group, 12% in the moderately food-insecure group, and 11.3% in the severely food-insecure group (p&#x2009;=&#x2009;0.013). The odds of obesity were 2.075 times higher among those experiencing severe food insecurity. The odds of severe food insecurity were 1.59 times higher in men and 2.50 times higher in rural residents, but 2.8 times lower in households with an income above the poverty line (Odds Ratio [OR]&#x2009;=&#x2009;0.356) and 1.87 times lower in those receiving social support (OR&#x2009;=&#x2009;0.532). Individuals with moderate and severe food insecurity were found to consume less protein-rich foods and more grain-based (carbohydrate) and snack products daily (p&#x2009;<&#x2009;0.001). Food insecurity was found to be a significant moderator in the relationship between protein intake and body mass index, with a stronger association observed at lower levels of food insecurity and a weaker association at higher levels. Food insecurity was associated with higher obesity prevalence, and this association was moderated by dietary patterns, specifically lower intake of protein-rich foods and higher consumption of cereals and snack foods. Providing social support to at-risk groups may help reduce obesity risk.

This study investigated the therapeutic effects of Yiguanjian on dry eye in rats and explored its underlying mechanism in regulating macrophage polarization. A rat model of dry eye was established by topical instillation of 0.2% benzalkonium chloride solution. After successful modeling, the rats were treated continuously for 4 weeks. Dry eye phenotypes were evaluated by the tear secretion test and corneal fluorescein staining. HE staining was performed to assess pathological changes in the cornea and lacrimal gland. PAS staining was employed to count conjunctival goblet cells. TUNEL staining was conducted to evaluate apoptosis. ELISA was employed to measure the levels of interleukin(IL)-1&#x3b2;, IL-6, IL-10, and tumor necrosis factor-&#x3b1;(TNF-&#x3b1;) in the lacrimal gland. Immunofluorescence assay was performed to detect the expression of phosphorylated nuclear factor-&#x3ba;B p65(p-NF-&#x3ba;B p65) in the cornea and to assess changes in the proportions of M1 and M2 macrophages in the lacrimal gland. RT-qPCR was employed to determine the mRNA levels of Toll-like receptor 4(TLR4) and myeloid differentiation factor 88(MyD88). Western blot analysis was performed to quantify the protein levels of TLR4, MyD88, inducible nitric oxide synthase(iNOS), cluster of differentiation 206(CD206), arginase-&#x2160;(Arg-&#x2160;), and NF-&#x3ba;B pathway-related proteins. The results showed that Yiguanjian increased tear secretion, alleviated corneal injury and the pathological changes in the cornea and lacrimal gland, increased conjunctival goblet cell number(P<0.05), and reduced the apoptotic rate(P<0.01) in the rat model of dry eye. In addition, Yiguanjian lowered the levels of IL-1&#x3b2;, IL-6, and TNF-&#x3b1; while increasing the level of IL-10 in the lacrimal gland(P<0.01), and it reduced the expression of p-NF-&#x3ba;B p65 in the corneal tissue(P<0.01), downregulated the expression of TLR4, MyD88, iNOS, and NF-&#x3ba;B pathway-related proteins(P<0.05), and upregulated the expression of CD206 and Arg-&#x2160;(P<0.05). Meanwhile, Yiguanjian decreased the proportion of M1 macrophages(P<0.05) and increased the proportion of M2 macrophages(P<0.01). These findings indicate that Yiguanjian can alleviate ocular surface injury and lacrimal gland inflammation in the rat model of dry eye by inhibiting TLR4/MyD88/NF-&#x3ba;B signaling pathway activation and promoting macrophage polarization from the M1 to the M2 phenotype.

This study aimed to investigate the differences in the ameliorative effects and underlying mechanisms of Buyang Huanwu Decoction(BHD) and its different ethanol elution fractions on pulmonary fibrosis(PF). The content of amygdalin, formononetin, kaempferol, ferulic acid and paeoniflorin in the drug-containing sera of BHD and its different fractions were determined using ultra-high-performance liquid chromatography-tandem quadrupole mass spectrometry. A rat model of PF was established by intratracheal instillation of bleomycin(BLM). The rats were divided into seven groups: a control group, a BLM group, a prednisone acetate(PA) group, a BHD group, a 30% ethanol elution fraction(Fr30) group, a 50% ethanol elution fraction(Fr50) group, and a 90% ethanol elution fraction(Fr90) group. All treatments were administered continuously for 21 days. The degrees of lung inflammation and fibrosis were observed by HE and Masson staining. The hydroxyproline(HYP) levels in lung tissue were determined using a HYP assay kit. The levels of interleukin-1&#x3b2;(IL-1&#x3b2;), interleukin-6(IL-6), interleukin-10(IL-10), tumor necrosis factor-&#x3b1;(TNF-&#x3b1;), and high mobility group box 1 protein(HMGB1) in lung tissue were determined using ELISA kits. The levels of total superoxide dismutase(T-SOD), malondialdehyde(MDA) and glutathione peroxidase(GSH-PX) in lung tissue were determined using corresponding commercial kits. Immunofluorescence staining and Western blot were used to detect the levels of epithelial-mesenchymal transition(EMT)-related proteins in lung tissue. RT-qPCR and Western blot were employed to determine the mRNA and protein levels of factors associated with the transforming growth factor-&#x3b2;1(TGF-&#x3b2;1)/Sma and Mad-related protein(Smad) pathway in lung tissue. The results showed that amygdalin was detected in the drug-containing sera of all groups, with the highest content in the Fr30 group and the lowest in the Fr90 group. Formononetin and kaempferol were detected in the BHD, Fr50, and Fr90 groups, with the highest content in the Fr50 group and the lowest in the Fr90 group. Ferulic acid was detected in all groups, with the highest content in the BHD group and the lowest in the Fr30 group. Paeoniflorin was only detected in the BHD and Fr30 groups, with similar content. Compared with the BLM group, the levels of HYP, TNF-&#x3b1;, IL-6, IL-1&#x3b2;, HMGB1, and MDA decreased in all treatment groups, while the levels of IL-10, T-SOD, and GSH-PX increased. However, there was no statistical significance in the changes of T-SOD level in the Fr30 group and HYP and IL-10 levels in the Fr90 group compared with the BLM group. Immunofluorescence staining showed a marked decrease in the protein expression of &#x3b1;-smooth muscle actin(&#x3b1;-SMA) in the lung tissue of the BHD, Fr30, Fr50, and Fr90 groups. Western blot analysis showed that the expression of epithelial cadherin(E-cadherin) significantly increased, while &#x3b1;-SMA and vimentin protein expressions significantly decreased in the lung tissue of the BHD, Fr30, Fr50, and Fr90 groups. RT-qPCR and Western blot analysis revealed that the mRNA and protein levels of TGF-&#x3b2;1 in the BHD and Fr30 groups significantly decreased, the phosphorylation(p)-Smad3/Smad3 ratio in all treatment groups significantly decreased, and the mRNA and protein levels of Smad7 in the BHD, Fr30 and Fr50 groups significantly increased. In conclusion, BHD and its different ethanol elution fractions may ameliorate BLM-induced PF in rats by inhibiting the TGF-&#x3b2;1/Smad pathway, with the Fr30 and Fr50 fractions showing better ameliorative effects.

Based on the "lung-gut axis" theory, this study explored the effects of Maxing Kugan Decoction(Mxd) on inflammation and intestinal barrier and flora in rats with bleomycin-induced idiopathic pulmonary fibrosis(IPF). A total of 24 male SD rats were randomly divided into four groups: a control group, a model group, a positive control group and an Mxd treatment group, with 6 rats in each group. After 5 days of quarantine and adaptive feeding, the IPF pathological model was induced by intratracheal instillation of bleomycin under laryngoscopic assistance in the model group, positive control group, and Mxd treatment group. Gastric gavage was initiated after successful modeling, and all SD rats were sacrificed on the 15th day post gavage. HE staining and Masson staining were used to observe histopathological changes of lung tissue, while HE staining was adopted to evaluate jejunal pathological changes. Enzyme-linked immunosorbent assay(ELISA) was performed to detect the serum levels of interleukin-1&#x3b2;(IL-1&#x3b2;), interleukin-6(IL-6), and tumor necrosis factor-&#x3b1;(TNF-&#x3b1;) in rats. AB-PAS staining was employed to determine the number of goblet cells in jejunal mucosal tissue. Immunofluorescence assay was used to detect the expression of zonula occludens-1(ZO-1) and occludin in rat jejunum, and 16S rDNA sequencing was conducted to analyze the intestinal microbiome of all rats. The results showed that the model group exhibited severe damage to jejunal mucosa and lung tissue accompanied by massive inflammatory cell infiltration, while the two treatment groups demonstrated partial structural defects with a small amount of inflammatory cell infiltration in the lungs and jejuna of rats. Compared with the control group, the model group showed significantly decreased body weight, number of goblet cells, and expression of ZO-1 and occludin proteins(P<0.01), while these indicators were notably increased after intervention in the two treatment groups(P<0.05 or P<0.01). According to 16S rDNA sequencing results, Mxd could regulate the richness and diversity of intestinal flora in rats. KEGG pathway analysis indicated that Mxd regulated pathways such as oxidative phosphorylation, amino sugar, and nucleotide sugar metabolism of intestinal flora in rats. In conclusion, the alteration of intestinal microbiome may be one of the potential mechanisms underlying the therapeutic effect of Mxd on IPF. Mxd can regulate the structure of intestinal microbiome, increase the abundance of beneficial bacteria, and reduce the number of harmful bacteria, as well as protect intestinal barrier and inhibit inflammatory response.

Glycemic control is a critical component in the management of diabetes mellitus among children and adolescents. This narrative review synthesizes existing evidence on the status of glycemic control-both good and poor-and its associated factors among Ethiopian children and adolescents living with diabetes. The objective of the review was to assess the pattern of glycemic control and identify factors associated with both good and poor glycemic outcomes among children and adolescents with diabetes in Ethiopia. Relevant studies reporting on glycemic control and associated factors were identified through searches conducted in Google Scholar, PubMed/MEDLINE, African Journals Online, and the Ethiopian Medical Journal. Additional grey literature sources were also reviewed. Eligible studies were screened and narratively synthesized. The prevalence of poor glycemic control among Ethiopian children and adolescents ranged from 39.3% to 89.3%. Conversely, good glycemic control was reported in 16.4% to 60.7% of participants. Factors associated with glycemic control included socio-demographic characteristics, treatment-related variables, health system constraints, and dietary habits. Poor glycemic control is widespread among Ethiopian children and adolescents with diabetes, underscoring the urgent need for improved management strategies and targeted interventions. Strengthening diabetes education, promoting self-monitoring of blood glucose, and improving access to essential medical supplies and insulin may help enhance glycemic outcomes.

The major histocompatibility complex (MHC) is an essential part of the adaptive immune systems that present antigenic peptides at the cell surface for recognition and activation of circulating T lymphocytes, which is vital for our body to recognize and respond to foreign pathogens, including viruses, bacteria, and cancerous cells. Human leukocyte antigen (HLA) genes encode proteins located on the surface of most cells in the body, and studies have shown that protein glycosylation plays a significant role in the folding of human leukocyte antigen (HLA) proteins, loading of peptides, and forming of HLA-peptide complex. In the meantime, some of those peptides presented by the MHC system are also glycosylated. Thus, glycosylation has a huge impact on cellular uptake, proteolytic processing, presentation by MHC, and subsequent T-cell priming. However, glycosylation characterization of the whole MHC system has often been neglected during conventional immunopeptidomics analysis due to the lower abundance of glycosylated peptides and increased complexity of the mass spectrum. To tackle this problem, we utilized hydrophilic interaction chromatography to enrich glycopeptides from both peptides bound to HLA and digest of HLA proteins that obtained from immunoprecipitation of MHC complex from cell lysate. Enriched glycopeptides are analyzed by mass spectrometry that enables the characterization of glycosylation of MHC by database search.

This study aimed to investigate the immunopharmacological mechanism of Saposhnikoviae Radix(SR) against respiratory viruses and bacteria infections based on immune signal activation. Mouse models of pneumonia induced by intranasal influenza A virus(H1N1) infection and intratracheal lipopolysaccharide(LPS) instillation were established. The effects of the water extract of SR on pulmonary CT imaging, histological damage, and inflammatory cytokine expression in lung tissues were evaluated. Using bone marrow-derived macrophages, this study analyzed the regulatory effects of the extract on macrophage proliferation and phagocytic function. RNA-seq and bioinformatics analysis, combined with molecular biology experiments, were employed to explore the regulatory role of the water extract of SR on the type &#x2160; interferon(IFN-&#x2160;) signaling pathway. The findings revealed that the water extract of SR significantly alleviated H1N1 infection-induced lung imaging and pathological damage in mice, reduced lung viral gene copies, and downregulated the expression of inflammatory cytokines such as interleukin-6(IL-6), tumor necrosis factor-&#x3b1;(TNF-&#x3b1;), and CXC motif chemokine ligand 10(CXCL10). Concurrently, drug treatment demonstrated similar lung tissue protective functions in the LPS-induced mouse pneumonia model. Cell experiments showed that the extract promoted proliferation of macrophages and enhanced their phagocytic capacity toward neutral red. Transcriptomic analysis revealed that genes upregulated by the extract of SR were significantly enriched in pathways including H1N1 infection, Toll-like receptor signaling, NOD-like receptor signaling, and IFN signaling. Finally, qRT-PCR and Western blot confirmed that the extract activated the interferon signaling pathway. In conclusion, the extract of SR activates innate immunity centered on IFN-&#x2160; signaling and enhances macrophage function, thereby improving the host's defense against viral and bacterial infections. It possesses potential preventive and therapeutic value for respiratory tract infection-associated pneumonia and lung injury.